This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately 40 million are infected with HIV-1. Worldwide 33% of HIV patients have chronic hepatitis C virus (HCV) infection and 10% of the HIV-infected population also have chronic hepatitis B (HBV). Almost 90% of intravenous drug users have HIV/HCV co-infection. The significance of such a proposal relates to the absence of an adequate animal model of hepatitis B and C, and co-infection of HIV-1,2 and hepatitis viruses, which represent the real situation in humans. The combination of two infections is related to a significant medical complication in the HIV-1-infected population. HCV, HBV and HIV infections are human infections, which cannot be distinguished in rodents. Thus, only by reconstitution of a mouse with a human immune system where the mouse liver has human hepatocytes will create an adequate model to study human immune response to viral antigens, thereby providing an excellent tool for vaccine development. This unique rodent model allows generation of data that previously could be obtained only in virally infected patients, limiting the necessity of further human studies.